The role of prostaglandins, prostacyclin and the products of lipoxygenase pathway of arachidonic acid metabolism will be studied in terms of the regulation of the circulation and blood pressure. These studies relate to: 1) the mechanism of action of angiotensin converting enzyme inhibitors in terms of prostaglandin-related mechanisms; 2) enzymic transformation of prostacyclin (PGI2) to a stable metabolite, 6-keto-PGE1 which may mediate effects previously ascribed to prostacyclin, such as inhibition of platelet aggregation and participation in the regulation of renin release; 3) the activity of PGE-9-ketoreductase, the enzyme which transforms PGE2 to PGF2 alpha within the kidney and the vasculature. Captopril, the antihypertensive drug, is being studied in spontaneously hypertensive rats and in isolated kidneys. The effects of captopril on vascular reactivity and blood pressure appear to be independent of changes in the activity of angiotensin converting enzyme and in prostaglandin-dependent vascular mechanisms. This has led to our studying the effects of captopril as related to the lipoxygenase pathway of arachidonic acid metabolism. A stable metabolite, 6-keto-PGE1, arising from prostacyclin in the liver, kidney, platelets, and blood vessels, has contributed to our understanding of the effects of prostacyclin on the circulation and on platelet function. The possibility should be considered that many of the effects of prostacyclin require conversion to 6-keto-PGE1 by 9-hydroxy-prostaglandin dehydrogenase-like enzymes. The activity of PGE-9-ketoreductase is very high in the rabbit kidney. It is responsible for conversion of 50% to 60% of the administered PGE2 to PGF2 alpha in the isolated kidney of the rabbit. The major site of PGE-9-ketoreductase is in the vascular compartment of the kidney where as much as 90% of the administered PGE2 can be converted to PGF2 alpha.